Skip to main content
Log in

Fucoidan from Sargassum wightii reduces oxidative stress through upregulating Nrf2/HO-1 signaling pathway in alloxan-induced diabetic cardiomyopathy rats

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Diabetic cardiomyopathy (DCM) is a form of cardiac dysfunction caused by diabetes, increasing heart failure and death. Studies shown that hyperglycemia-induced oxidative stress significantly affects heart structure and functional changes during diabetic cardiomyopathy. Fucoidans are sulfated polysaccharide derived from naturally available seaweeds and reported for various biological functions such as antioxidant, anti-diabetic, and anti-inflammatory. However, the therapeutic potential of Indian seaweeds against DCM remains largely unexplored. Therefore, the current study aimed to work on the cardioprotective effect of extracted fucoidan from Sargassum wightii (SwF) in alloxan-induced DCM.

Methods and results

Diabetes (DM) was induced with alloxan monohydrate (150 mg/kg−1) dissolved in Nacl (0.9%) overnight–fasted rats. Group III, IV rats were DM induced, followed by treated with SwF (150 mg/kg−1) and (300 mg/kg−1). Group V and VI were non-diabetic rats and received SwF (150 mg/kg−1) and (300 mg/kg−1). SwF reduced classical progressive DM complications such as hyperglycemia, polydipsia, polyphagia, and polyurea in alloxan-induced diabetic rats. Biochemical analysis showed that SwF decreased blood glucose, cardiac markers enzymes, and lipid peroxidation levels compared to diabetic rats. SwF administration significantly increased Nrf2, HO-1, SOD, Catalase, and NQO1 gene expression. In addition, SwF-treated rats showed reduced heart tissue damage with increased Nrf2 and HO-1 protein expression.

Conclusion

The current research concludes that targeting oxidative stress with SwF provided an effective role in the prevention of DCM. Thus, fucoidan could be used to develop functional food ingredients for DCM.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The authors declare that all data supporting the findings of this study are available within the article and its supplementary information files.

References

  1. Dillmann WH (2019) Diabetic cardiomyopathy: what is it and can it be fixed? Circul Res 124:1160–1162. https://doi.org/10.1161/CIRCRESAHA.118.314665

    Article  CAS  Google Scholar 

  2. Jia G, Hill MA, Sowers JR (2018) Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ Res 122:624–638. https://doi.org/10.1161/CIRCRESAHA.117.311586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Booz GW, Baker KM (1995) Molecular signalling mechanisms controlling growth and function of cardiac fibroblasts. Cardiovasc Res 30:537–543

    Article  CAS  PubMed  Google Scholar 

  4. Isfort M, Stevens SC, Schaffer S, Jong CJ, Wold LE (2014) Metabolic dysfunction in diabetic cardiomyopathy. Heart Fail Rev 19:35–48. https://doi.org/10.1007/s10741-013-9377-8

    Article  CAS  PubMed  Google Scholar 

  5. De Geest B, Mishra M (2022) Role of oxidative stress in diabetic cardiomyopathy. Antioxid (Basel 11:784. https://doi.org/10.3390/antiox11040784

    Article  CAS  Google Scholar 

  6. Tsutsui H, Kinugawa S, Matsushima S (2011) Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol 301:H2181–H2190. https://doi.org/10.1152/ajpheart.00554.2011

    Article  CAS  PubMed  Google Scholar 

  7. Ge Z-D, Lian Q, Mao X, Xia Z (2019) Current status and challenges of NRF2 as a potential therapeutic target for diabetic cardiomyopathy. Int Heart J 60:512–520. https://doi.org/10.1536/ihj.18-476

    Article  CAS  PubMed  Google Scholar 

  8. Parim B, Sathibabu Uddandrao VV, Saravanan G (2019) Diabetic cardiomyopathy: molecular mechanisms, detrimental effects of conventional treatment, and beneficial effects of natural therapy. Heart Fail Rev 24:279–299. https://doi.org/10.1007/s10741-018-9749-1

    Article  PubMed  Google Scholar 

  9. Afonso NC, Catarino MD, Silva AMS, Cardoso SM (2019) Brown macroalgae as valuable food ingredients. Antioxid (Basel) 8:365. https://doi.org/10.3390/antiox8090365

    Article  CAS  Google Scholar 

  10. Liu L, Heinrich M, Myers S, Dworjanyn SA (2012) Towards a better understanding of medicinal uses of the brown seaweed Sargassum in Traditional Chinese Medicine: a phytochemical and pharmacological review. J Ethnopharmacol 142:591–619. https://doi.org/10.1016/j.jep.2012.05.046

    Article  PubMed  Google Scholar 

  11. Ale MT, Meyer AS (2013) Fucoidans from brown seaweeds: an update on structures, extraction techniques and use of enzymes as tools for structural elucidation. RSC Adv 3:8131–8141. https://doi.org/10.1039/C3RA23373A

    Article  CAS  Google Scholar 

  12. Li B, Lu F, Wei X, Zhao R (2008) Fucoidan: structure and bioactivity. Molecules 13:1671–1695. https://doi.org/10.3390/molecules13081671

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ji Y, Jin D, Qi J, Wang X, Zhang C, An P, Luo Y, Luo J (2022) Fucoidan protects against doxorubicin-Induced cardiotoxicity by reducing oxidative stress and preventing mitochondrial function Injury. Int J Mol Sci. https://doi.org/10.3390/ijms231810685

    Article  PubMed  PubMed Central  Google Scholar 

  14. Chang PM, Li KL, Lin YC (2019) Fucoidan(-)Fucoxanthin ameliorated cardiac function via IRS1/GRB2/ SOS1, GSK3beta/CREB pathways and metabolic pathways in senescent mice. Mar Drugs. https://doi.org/10.3390/md17010069

    Article  PubMed  PubMed Central  Google Scholar 

  15. Yu X, Zhang Q, Cui W, Zeng Z, Yang W, Zhang C, Zhao H, Gao W, Wang X, Luo D (2014) Low molecular weight fucoidan alleviates cardiac dysfunction in diabetic Goto-Kakizaki rats by reducing oxidative stress and cardiomyocyte apoptosis. J Diabetes Res 2014:420929. https://doi.org/10.1155/2014/420929

    Article  PubMed  PubMed Central  Google Scholar 

  16. Lin Z, Wang F, Yan Y, Jin J, Quan Z, Tong H, Du J (2023) Fucoidan derived from Sargassum pallidum alleviates metabolism disorders associated with improvement of cardiac injury and oxidative stress in diabetic mice. Phytother Res. https://doi.org/10.1002/ptr.7901

    Article  PubMed  Google Scholar 

  17. Chotigeat W, Tongsupa S, Supamataya K, Phongdara A (2004) Effect of fucoidan on disease resistance of black tiger shrimp. Aquaculture 233:23–30. https://doi.org/10.1016/j.aquaculture.2003.09.025

    Article  CAS  Google Scholar 

  18. Puhari SSM, Yuvaraj S, Vasudevan V, Ramprasath T, Rajkumar P, Arunkumar K, Amutha C, Selvam GS (2022) Isolation and characterization of fucoidan from four brown algae and study of the cardioprotective effect of fucoidan from Sargassum wightii against high glucose-induced oxidative stress in H9c2 cardiomyoblast cells. J Food Biochem 46:e14412. https://doi.org/10.1111/jfbc.14412

    Article  CAS  PubMed  Google Scholar 

  19. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358. https://doi.org/10.1016/0003-2697(79)90738-3

    Article  CAS  PubMed  Google Scholar 

  20. Mahmoud AM (2017) Exercise amaliorates metabolic disturbances and oxidative stress in diabetic cardiomyopathy: possible underlying mechanisms. Adv Exp Med Biol 999:207–230. https://doi.org/10.1007/978-981-10-4307-9_12

    Article  PubMed  Google Scholar 

  21. Mohan M, Dihoum A, Mordi IR, Choy AM, Rena G, Lang CC (2021) Left ventricular hypertrophy in diabetic cardiomyopathy: a target for intervention. Front Cardiovasc Med 8:746382. https://doi.org/10.3389/fcvm.2021.746382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Ganesan K, Rana MBM, Sultan S (2018) Oral hypoglycemic medications. StatPearls Publishing, StatPearls

    Google Scholar 

  23. Saraswati, Giriwono PE, Iskandriati D, Andarwulan N (2021) Screening of In-Vitro anti-inflammatory and antioxidant activity of Sargassum ilicifolium crude lipid extracts from different coastal areas in Indonesia. Mar Drugs. https://doi.org/10.3390/md19050252

    Article  PubMed  PubMed Central  Google Scholar 

  24. Zhang C, Jia J, Zhang P, Zheng W, Guo X, Ai C, Song S (2022) Fucoidan from Laminaria japonica ameliorates type 2 diabetes mellitus in association with modulation of gut microbiota and metabolites in streptozocin-treated mice. Foods. https://doi.org/10.3390/foods12010033

    Article  PubMed  PubMed Central  Google Scholar 

  25. Wang X, Shan X, Dun Y, Cai C, Hao J, Li G, Cui K, Yu G (2019) Anti-metabolic syndrome effects of fucoidan from Fucus vesiculosus via reactive oxygen species-mediated regulation of JNK, akt, and AMPK signaling. Molecules. https://doi.org/10.3390/molecules24183319

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ren D, Wang Q, Yang Y, Hu Y, Song Y, He Y, Liu S, Wu L (2019) Hypolipidemic effects of fucoidan fractions from Saccharina sculpera (Laminariales, Phaeophyceae). Int J Biol Macromol 140:188–195. https://doi.org/10.1016/j.ijbiomac.2019.08.002

    Article  CAS  PubMed  Google Scholar 

  27. Mythili S, Malathi N (2015) Diagnostic markers of acute myocardial infarction. Biomed Rep 3:743–748. https://doi.org/10.3892/br.2015.500

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lekshmi VS, Rauf AA, Kurup GM (2019) Sulfated polysaccharides from the edible marine algae Padina tetrastromatica attenuates isoproterenol-induced oxidative damage via activation of PI3K/Akt/Nrf2 signaling pathway - an in vitro and in vivo approach. Chem Biol Interact 308:258–268. https://doi.org/10.1016/j.cbi.2019.05.044

    Article  CAS  Google Scholar 

  29. Radenkovic M, Stojanovic M, Prostran M (2016) Experimental diabetes induced by alloxan and streptozotocin: the current state of the art. J Pharmacol Toxicol Methods 78:13–31. https://doi.org/10.1016/j.vascn.2015.11.004

    Article  CAS  PubMed  Google Scholar 

  30. Wang Y, Feng W, Xue W, Tan Y, Hein DW, Li XK, Cai L (2009) Inactivation of GSK-3beta by metallothionein prevents diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling. Diabetes 58:1391–1402. https://doi.org/10.2337/db08-1697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Abdel-Daim MM, Abushouk AI, Bahbah EI, Bungau SG, Alyousif MS, Aleya L, Alkahtani S (2020) Fucoidan protects against subacute diazinon-induced oxidative damage in cardiac, hepatic, and renal tissues. Environ Sci Pollut Res Int 27:11554–11564. https://doi.org/10.1007/s11356-020-07711-w

    Article  CAS  PubMed  Google Scholar 

  32. Kobayashi M, Yamamoto M (2005) Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxid Redox Signal 7:385–394. https://doi.org/10.1089/ars.2005.7.385

    Article  CAS  PubMed  Google Scholar 

  33. Li B, Liu S, Miao L, Cai L (2012) Prevention of diabetic complications by activation of Nrf2: diabetic cardiomyopathy and nephropathy. Exp Diabetes Res. https://doi.org/10.1155/2012/216512

    Article  PubMed  PubMed Central  Google Scholar 

  34. El-Omar MM, Yang ZK, Phillips AO, Shah AM (2004) Cardiac dysfunction in the Goto-Kakizaki rat. A model of type II diabetes mellitus. Basic Res Cardiol 99:133–141. https://doi.org/10.1007/s00395-004-0440-4

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Shanavas Syed Mohamed Puhari expresses his gratitude to the UGC BSR fellowship program, New Delhi, India. The authors also thank, UGC-CEGS, UGC-CAS, UGC-NRCBS, DST PURSE and DST-FIST program for the central instrumentation facility at SBS, MKU.

Funding

The authors declare that no grants were received during the preparation of this manuscript.

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization—SSMP, GSS; Methodology—SSMP, SY, VV; Formal analysis—SSMP, TR, GSS; Investigation—SSMP, SY, VV; Writing - Original draft – SSMP, SY; Review and Editing – SSMP, SY, VV, TR, KA, CA and GSS; Funding acquisition – GSS.

Corresponding author

Correspondence to Govindan Sadasivam Selvam.

Ethics declarations

Competing interests

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

The experimental procedure was approved by the Internal Research and Review Board, Ethical Clearance, Biosafety and Animal Welfare Committee of Madurai Kamaraj University.

Consent to publish

All authors have contributed significantly and agree with publication the content of the paper.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 14 kb)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Puhari, S.S.M., Yuvaraj, S., Vasudevan, V. et al. Fucoidan from Sargassum wightii reduces oxidative stress through upregulating Nrf2/HO-1 signaling pathway in alloxan-induced diabetic cardiomyopathy rats. Mol Biol Rep 50, 8855–8866 (2023). https://doi.org/10.1007/s11033-023-08780-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-023-08780-z

Keywords

Navigation